MODEL STUDIES OF HYDROPORPHYRIN-CONTAINING ENZYMES

本研究项目的目的是了解 的结构，电子和机械特征， 含氢卟啉的酶。 这些催化关键步骤 包括无机碳、氮和硫在内的代谢过程 循环和微生物的许多主要能量产生途径。 该计划有两个具体目标：（1）确定重要的 氢卟啉络合物性质的差异， 卟啉和其他四吡咯，以及（2）开发反应性模型 甲基辅酶M还原酶的F430依赖性还原裂解 甲烷。 酶活性位点的合成小分子类似物 和辅基将用于这些研究。 第一 目的将通过检验卟啉， 氢卟啉、咕啉和其它四吡咯的区别在于 它们的灵活性和最佳孔尺寸和孔尺寸范围 在它们的络合物中容易获得， 立体化学可以调节大环化合物的性质。 的 假设将通过检查化学过程进行测试， 金属离子半径的变化或四吡咯的变形 大循环 饱和度和取代基的影响 大环在轴向连接平衡上的立体化学和 大半径金属离子如Ni（I）和Cu（I）的可及性将是 研究了 面外柔度将通过研究来探讨 大环饱和度对芳基势垒的影响 N-取代四芳基氢化卟啉的环旋转 R-Co（P）L的钴-烷基键离解能的关联 与大环P和反式配体L的空间体积一起。 的 第二个目标将通过探索NiI（OEiBC）的反应来实现。 重点将放在确定氢化物物种的作用， NiI化学（OEiBC），检查镍络合物的能力， 裂解硫醚，如甲基辅酶M，并检测烷基镍 和镍-镍OEiBC配合物。

The objective of this research program is to develop an understanding of the structural, electronic, and mechanistic features of the hydroporphyrin-containing enzymes. These catalyze important steps in key metabolic processes including the inorganic carbon, nitrogen, and sulfur cycles and many of the main energy producing pathways of microorganisms. The program has two specific aims: (1) to determine the significant differences in the properties of the complexes of hydroporphyrins, porphyrins, and other tetrapyrroles and (2) to develop a reactivity model for the F430 dependent reductive cleavage of methyl coenzyme M reductase to methane. Synthetic, small molecule analogues of enzyme active sites and prosthetic groups will be used in these investigations. The first aim will be addressed by testing the hypotheses that porphyrin, hydroporphyrins, corrins, and other tetrapyrroles are distinguished by their flexibility and by the optimal hole size and range of hole sizes readily accessible in their complexes and that the substituent stereochemistry can modulate the properties of the macrocycle. The hypotheses will be tested by examining chemical processes that require changes in metal ion radius or deformation of the tetrapyrrole macrocycle. The effect of the saturation level and substituent stereochemistry of the macrocycle on axial ligation equilibria and the accessibility of large radius metal ions like Ni(I) and Cu(I) will be investigated. Out-of-plane flexibility will be probed by investigations of the effect of the macrocycle saturation level on the barrier to aryl ring rotation in N-substituted tetraarylhydroporphyrins and by correlations of the cobalt-alkyl bond dissociation energies of R-Co(P)L with the macrocycle, P, and the steric bulk of the trans ligand, L. The second aim will be achieved by exploring the reactions of NiI(OEiBC). Emphasis will be placed on determining the role of hydride species in the chemistry of NiI(OEiBC), examining the ability of nickel complexes to cleave thioethers like methyl coenzyme M, and the detection of alkyl-Ni and hydrido-Ni OEiBC complexes.